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Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.

Publication ,  Journal Article
Wiehe, K; Bradley, T; Meyerhoff, RR; Hart, C; Williams, WB; Easterhoff, D; Faison, WJ; Kepler, TB; Saunders, KO; Alam, SM; Bonsignori, M; Haynes, BF
Published in: Cell Host Microbe
June 13, 2018

HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. One bottleneck for induction of bnAbs is the evolution of viral envelopes (Envs) that can select bnAb B cell receptors (BCR) with improbable mutations. Here we define the probability of bnAb mutations and demonstrate the functional significance of key improbable mutations in three bnAb B cell lineages. We show that bnAbs are enriched for improbable mutations, which implies that their elicitation will be critical for successful vaccine induction of potent bnAb B cell lineages. We discuss a mutation-guided vaccine strategy for identification of Envs that can select B cells with BCRs that have key improbable mutations required for bnAb development.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

June 13, 2018

Volume

23

Issue

6

Start / End Page

759 / 765.e6

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Probability
  • Mutation Rate
  • Mutation
  • Immunology
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Cytidine Deaminase
 

Citation

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Wiehe, K., Bradley, T., Meyerhoff, R. R., Hart, C., Williams, W. B., Easterhoff, D., … Haynes, B. F. (2018). Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6), 759-765.e6. https://doi.org/10.1016/j.chom.2018.04.018
Wiehe, Kevin, Todd Bradley, R Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, et al. “Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.Cell Host Microbe 23, no. 6 (June 13, 2018): 759-765.e6. https://doi.org/10.1016/j.chom.2018.04.018.
Wiehe K, Bradley T, Meyerhoff RR, Hart C, Williams WB, Easterhoff D, et al. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe. 2018 Jun 13;23(6):759-765.e6.
Wiehe, Kevin, et al. “Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.Cell Host Microbe, vol. 23, no. 6, June 2018, pp. 759-765.e6. Pubmed, doi:10.1016/j.chom.2018.04.018.
Wiehe K, Bradley T, Meyerhoff RR, Hart C, Williams WB, Easterhoff D, Faison WJ, Kepler TB, Saunders KO, Alam SM, Bonsignori M, Haynes BF. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe. 2018 Jun 13;23(6):759-765.e6.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

June 13, 2018

Volume

23

Issue

6

Start / End Page

759 / 765.e6

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Probability
  • Mutation Rate
  • Mutation
  • Immunology
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Cytidine Deaminase